Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study
Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study
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DOI：
10.1093/neuonc/nop047
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发表时间：
2010-04-01
期刊：
影响因子：
15.9
通讯作者：
Carpentier, Antoine F.
中科院分区：
文献类型：
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作者：
Carpentier, Alexandre;Metellus, Philippe;Carpentier, Antoine F.
含有 CpG 基序 (CpG-ODN) 的免疫刺激寡脱氧核苷酸在局部注射时在癌症模型中显示出良好的功效。在一项 I 期临床试验中，胶质母细胞瘤 (GBM) 患者瘤内输注 CpG-ODN 的耐受性良好，剂量高达 20 mg。该 II 期试验旨在研究 CpG-ODN 局部治疗对复发性 GBM 患者的疗效。放疗后至少 3 个月出现复发性 GBM 且之前接受过 1 或 2 种化疗方案的患者通过对流增强给药方式接受 20 mg CpG-ODN (CpG-28)。主要终点是纳入后 6 个月内没有肿瘤进展的患者百分比。次要终点是耐受性、生存率和放射学反应。 2004年11月至2006年3月期间，两个中心招募了34名患者。其中31名患者接受了CpG-ODN治疗。 6 个月时的无进展生存率 (PFS) 为 19%。观察到 1 例部分反应和 3 例轻微反应。中位总生存期为 28 周。 8 名患者（24%）在纳入后 1 年内存活，5 名患者（15%）在 2 年后存活。治疗通常耐受性良好。正如之前报道的，最常见的毒性是淋巴细胞减少、轻度发烧、癫痫发作和短暂的神经功能恶化。尽管少数病例表现出放射学反应，但 CpG-28 在该患者群体中的 6 个月 PFS 中表现出适度的活性。可能从这种方法中受益的亚组患者的分子或临床特征仍有待确定。
Immunostimulating oligodeoxynucleotides containing CpG motifs (CpG-ODN) have shown promising efficacy in cancer models when injected locally. In a phase I clinical trial, intratumoral infusions of CpG-ODN in glioblastoma (GBM) patients were well tolerated at doses up to 20 mg. This phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with recurrent GBMs. Patients with recurrent GBM occurring at least 3 months after radiotherapy, and previously treated with 1 or 2 regimens of chemotherapy received 20 mg of CpG-ODN (CpG-28) by convection-enhanced delivery. The primary endpoint was the percentage of patients without tumor progression 6 months after inclusion. Secondary endpoints were tolerance, survival, and radiological response. Thirty-four patients were enrolled in two centers between November 2004 and March 2006. Thirty-one patients received CpG-ODN treatment. The progression-free survival (PFS) at 6 months was 19%. One partial response and 3 minor responses were observed. The median overall survival was 28 weeks. Eight patients (24%) were alive 1 year after inclusion and 5 patients (15%) were alive after 2 years. Treatment was usually well tolerated. As reported previously, the most common toxicities were lymphopenia, mild fever, seizures, and transient neurological worsening. Despite a few cases showing a radiological response, CpG-28 showed modest activity on the 6-month PFS in this patient population. The molecular or clinical characteristics of a subgroup of patients that could potentially benefit from such an approach remain to be defined.